Increased sympathetic activity and reduced vagal activity are associated with increased mortality both after myocardial infarction and in heart failure; furthermore, vagal withdrawal has been documented to precede acute decompensation. Experimental studies indicate that increased parasympathetic activity by means of vagal stimulation may reduce mortality in animal models of post-infarction sudden cardiac death and of chronic heart failure. Initial clinical results demonstrate that chronic vagus nerve stimulation in heart failure patients with severe systolic dysfunction appears to be safe and tolerable and may improve quality of life, submaximal exercise capacity, and LV function. Vagus nerve stimulation derives these potential clinical benefits from multiple mechanisms of action. These include reduced heart rate, restoration of heart rate variability and baroreflex sensitivity, suppression of pro-inflammatory cytokines, and antiarrhythmic effects.